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Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models
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Journal Article
Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models
2019
Overview
Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca
2+
-dependent protein that promotes NF-κB-dependent endothelial cell activation,
Ccl2
induction and Ly6C
+
CCR2
+
monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of
Anxa6
in cancer cells or
Ccr2
in host cells blunts the pro-metastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy.
Keklikoglou et al. report that cytotoxic drugs induce tumour-derived extracellular vesicles that facilitate monocyte expansion through annexin A6 and thus lung metastasis in breast cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 13/44
/ 13/95
/ 14/19
/ 14/28
/ 14/35
/ 631/67
/ 64/116
/ 64/60
/ 82/58
/ Animals
/ Biomedical and Life Sciences
/ Calcium
/ Cancer
/ Complications and side effects
/ Doxorubicin - therapeutic use
/ Exosomes
/ Extracellular Vesicles - drug effects
/ Extracellular Vesicles - metabolism
/ Female
/ Humans
/ Lung Neoplasms - drug therapy
/ Lungs
/ Mammary Neoplasms, Experimental - drug therapy
/ Mammary Neoplasms, Experimental - metabolism
/ Mammary Neoplasms, Experimental - pathology
/ Monocyte chemoattractant protein 1
/ Organs
/ Paclitaxel - therapeutic use
/ Proteins
/ Taxanes
/ Tumors
/ Vesicles
